Patients with well-documented chronic hepatitis C are being evaluated to determine the long-term natural history of this common form of chronic liver disease. A cohort of such patients are available to evaluate experimental therapies. Previous studies have shown that alpha interferon therapy has a short-term beneficial effect in approximately 50 per cent of patients. This response is sustained in approximately 10-15 per cent after stopping interferon. A randomized, placebo-controlled trial of ribavirin showed that a 1 year course of this nucleoside analogue is associated with significant improvement in serum aminotransferase activities and in hepatic lobular necrosis despite unchanged serum levels of HCV RNA. Continous ribavirin therapy for up to 2 years demonstrated the practicality of long term supressive therapy in this disease. A controlled trial of the combination of ribavirin and interferon has been initiated. Patients who do not respond will be continued on therapy with ribavirin alone or placebo to assess whether long term therapy with ribavirin can improve chronic hepatitis C in patients resistant to all therapies.